Impact of a New Preoperative Stratification Based on Cardiac Structural Compromise in Patients with Severe Aortic Stenosis Undergoing Valve Replacement Surgery.

Introduction and objectives: Aortic valve replacement surgery (SAVR) remains a recommended indication, though its pre-surgical stratification is an ongoing challenge. Despite the widespread use of scores like the STS and EuroSCORE II, they have a number of limitations, while often neglecting structural parameters like left ventricular hypertrophy or left atrium volume. This study aimed to evaluate whether a new adaptation of the Généreux classification in the preoperative risk stratification of severe aortic stenosis (AS) is associated with the primary outcome, and to compare it with the original classification versus the traditional scores in short- and long-term follow-up. Methods: We conducted a retrospective, single-center study involving patients with confirmed severe AS who underwent SAVR. The new stratification categorized patients into three stages. Cox regression analyses were conducted to identify factors associated with mortality, with survival analysis performed using Kaplan-Meier curves. A p-value < 0.05 was considered statistically significant. Results: A total of 508 patients were included. Stage 3 patients had a lower median age (67 years). The median EuroSCORE II and STS scores were 2.75 and 2.62%, respectively (p ≤ 0.001). Over a median follow-up of 81 months, 56 deaths occurred (11%). Kaplan-Meier curve analysis revealed significant differences in all-cause mortality among the three groups (HR 4.073, log-rank p ≤ 0.001). Multivariable analysis identified the three preoperative stages (HR 3.22, [95% CI 1.44-7.20], p = 0.004) and mean transaortic gradient (HR 0.96, [95% CI 0.92-0.99], p = 0.021) as independent variables of mortality. The original Généreux scale AUC was higher (AUC: 0.760, 95% CI: 0.692-0.829) compared to the modified Généreux scale (AUC: 0.758, 95% CI: 0.687-0.829). However, no statistical differences were found between the different scales. Conclusions: Preoperative three-stage classification and low transaortic gradient are factors associated with increased all-cause mortality in patients undergoing SAVR. The proposed staging system performed better in the mortality analysis than EuroSCORE II and STS and was similar to the original classification.

Tissue-resident memory T cells: Harnessing their properties against infection for cancer treatment.

We have rapidly gained insights into the presence and function of T lymphocytes in non-lymphoid tissues, the tissue-resident memory T (TRM) cells. The central pillar of adaptive immunity has been expanded from classic central memory T cells giving rise to progeny upon reinfection and effector memory cells circulating through the blood and patrolling the tissues to include TRM cells that reside and migrate inside solid organs and tissues. Their development and maintenance have been studied in detail, providing exciting clues on how their unique properties used to fight infections may benefit therapies against solid tumors. We provide an overview of CD8 TRM cells and the properties that make them of interest for vaccination and cancer therapies.

Sarcoidosis-Like Reaction After Chemotherapy Mimicking Metastasis in a Patient With Two Synchronous Tumors: A Case Report.

Sarcoidosis presents a diagnostic challenge due to its diverse clinical manifestations and potential to mimic malignancies. We report a clinical case involving a 46-year-old woman diagnosed with localized synchronous ovarian and endometrial carcinomas treated with surgery. Following adjuvant chemotherapy and radiotherapy, the patient developed suspicious pulmonary micronodules and lymphadenopathy observed in imaging studies, raising concerns about cancer recurrence. Histopathological analysis revealed chronic granulomatous inflammation without evidence of malignancy, leading to a diagnosis of a sarcoidosis-like reaction secondary to chemotherapy. Remarkably, these lesions resolved spontaneously without specific intervention. This case emphasizes the importance of a multidisciplinary approach in managing complex oncological presentations and underscores the significance of histopathological examination in distinguishing between malignancy and chemotherapy-induced sarcoidosis-like reactions.

Impact of TNFRSF1B (rs3397, rs1061624 and rs1061622) and IL6 (rs1800796, rs1800797 and rs1554606) Gene Polymorphisms on Inflammatory Response in Patients with End-Stage Kidney Disease Undergoing Dialysis.

We aimed to study the impact of polymorphisms in the genes encoding interleukin-6 (IL6) and tumor necrosis factor receptor-2 (TNFR2), reported to be mortality risk predictors, in patients with end-stage kidney disease (ESKD) undergoing dialysis. TNFRSF1B (rs3397, rs1061624, and rs1061622) and IL6 (rs1800796, rs1800797, and rs1554606) polymorphisms were studied in patients with ESKD and controls; the genotype and allele frequencies and the associations with inflammatory and erythropoiesis markers were determined; deaths were recorded throughout the following two years. The genotype and allele frequencies for the TNFRSF1B rs3397 polymorphism were different in these patients compared to those in the controls and the global and European populations, and patients with the C allele were less common. Patients with the CC genotype for TNFRSF1B rs3397 presented higher hemoglobin and erythrocyte counts and lower TNF-α levels, suggesting a more favorable inflammatory response that seems to be associated with erythropoiesis improvement. Patients with the GG genotype for TNFRSF1B rs1061622 showed lower serum ferritin levels. None of the TNFRSF1B (rs3397, rs1061624, and rs1061622) or IL6 (rs1800796, rs1800797, and rs1554606) polymorphisms had a significant impact on the all-cause mortality rate of Portuguese patients with ESKD.

Therapeutic potential of LINS01 histamine H3 receptor antagonists as antineoplastic agents for triple negative breast cancer.

The aims of this work were to evaluate the expression of histamine H3 receptor (H3R) in triple negative breast cancer (TNBC) samples and to investigate the antitumoral efficacy and safety of the LINS01 series of H3R antagonists, through in silico, in vitro, and in vivo approaches. Antitumor activity of LINS01009, LINS01010, LINS01022, LINS01023 was assayed in vitro in 4T1 and MDA-MB-231 TNBC cells (0.01-100 µM), and in vivo in 4T1 tumors orthotopically established in BALB/c mice (1 or 20 mg/kg). Additionally, H3R expression was assessed in 50 human TNBC samples. We have described a higher H3R mRNA expression in basal-like/TNBC tumors vs. matched normal tissue using TCGA Pan-Cancer Atlas data, and a higher H3R expression in human tumor samples vs. peritumoral tissue evidenced by immunohistochemistry associated with poorer survival. Furthermore, while all the essayed compounds showed antitumoral properties, LINS01022 and LINS01023 exhibited the most potent antiproliferative effects by: i) inducing cell apoptosis and suppressing cell migration in 4T1 and MDA-MB-231 TNBC cells, and ii) inhibiting cell growth in paclitaxel-resistant 4T1 cells (potentiating the paclitaxel antiproliferative effect). Moreover, 20 mg/kg LINS01022 reduced tumor size in 4T1 tumor-bearing mice, exhibiting a safe toxicological profile and potential for druggability estimated by ADME calculations. We conclude that the H3R is involved in the regulation of TNBC progression, offering promising therapeutic potential for the novel LINS01 series of H3R antagonists.

The histamine H4 receptor antagonist 1-[(5-chloro-2,3-dihydro-1-benzofuran-2-yl)methyl]-4-methyl-piperazine(LINS01007) prevents the development of DSS-induced colitis in mice.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with growing incidence worldwide. Our group reported the compound 5-choro-1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazine (LINS01007) as H4R antagonist (pKi 6.2) and therefore the effects and pharmacological efficacy on a DSS-induced mice model of UC were assessed in this work. Experimental acute colitis was induced in male BALB/c mice (n = 5-10) by administering 3 % DSS in the drinking water for six days. The test compound LINS01007 was administered daily i.p. (5 mg/kg) and compared to control group without treatment. Body weight, water and food consumption, and the presence of fecal blood were monitored during 7-day treatment period. The levels of inflammatory markers (PGE2, COX-2, IL-6, NF-κB and STAT3) were also analyzed. Animals subjected to the acute colitis protocol showed a reduction in water and food intake from the fourth day (p < 0.05) and these events were prevented by LINS01007. Histological signs of edema, hyperplasia and disorganized intestinal crypts, as well as neutrophilic infiltrations, were found in control mice while these findings were significantly reduced in animals treated with LINS01007. Significant reductions in the levels of PGE2, COX-2, IL-6, NF-κB and STAT3 were observed in the serum and tissue of treated animals. The results demonstrated the significant effects of LINS01007 against DSS-induced colitis, highlighting the potential of H4R antagonism as promising treatment for this condition.

Clinical and thermographic evaluation after lower third molar extractions and the application of different photobiomodulation protocols: double-blind randomised clinical trial.

OBJECTIVES: to compare the parameters of pain, oedema, temperature, and soft tissue closure in dental sockets that received two different photobiomodulation (PBM) protocols following extractions. MATERIALS AND METHODS: Thirty-one participants had their teeth 38 and 48 extracted. Subsequently, one of the dental sockets received PBM at a wavelength (WL) of 808 nanometers (808 group- nm) and the other dental socket received the PBM at WLs of 808 nm and 660 nm, simultaneously (808 + 660 group). The PBM was applied immediately after the surgical procedure and on the 3rd and 7th days. RESULTS: The mean of Visual Analogue Scale (VAS) values for pain were 1.45 for the 3rd day and 0.52 for the 7th day in the 808 + 660 and 808 group, respectively. The mean the pogonion-tragus measurement, used to assess facial oedema on the 3rd day, was 15.38 cm (range 13.5-17.5) in the 808 + 660 group and 15.48 cm (range 14.0-17.5) in the 808 group. The mean facial temperatures in the 808 + 660 group were 34.9 degrees Celsius (ºC) (range 33.5-36.4) on the 3rd day and 35 ºC (range 33.4-36.4) on the 7th day. In the 808 group, the mean temperatures were 34.9 ºC (range 33.9-36.2) on the 3rd day and 34.9 ºC (33.7-36.2) on the 7th day. Regarding the dimensions of the dental socket, the mean were similar for both groups. Significant differences between the groups were only observed in the pain parameter and only on the 7th day, being greater for the 808 + 660 group (p = 0.031). CONCLUSIONS: The association of the 660 nm with 808 nm, and the increase in energy did not showed more benefits in pain reduction oedema, or acceleration of the closure of the soft tissues of the dental sockets of lower third molars, in the protocols used here. CLINICAL RELEVANCE: There is no need to combine lasers at wavelengths of 660 and 808 nm to reduce oedema, pain and repair of soft tissues after extraction of lower third molars. CLINICAL TRIAL REGISTRATION: This trial was registered in the Brazilian Registry of Clinical Trials (ReBEC) with the following code: RBR-66pyrh8, on 29th December, 2022.

Antioxidant activity of an Mg(II) compound containing ferulic acid as a chelator: potential application for active packaging and riboflavin stabilisation.

Foods rich in riboflavin (Rf) are susceptible to degradation due to oxidative processes with the formation of radicals. Herein, we describe the features and stability of an Mg(II) complex containing ferulic acid (fer) and 1,10-phenanthroline (phen) as chelators: henceforth called Mg(phen)(fer). The electrochemical behavior of Mg(phen)(fer) is pH dependent and results from the stabilisation of the corresponding phenoxyl radical via complexation with Mg(II). This stabilisation enhances the antioxidant activity of Mg(phen)(fer) with respect to free fer and commercial antioxidants. Mg(phen)(fer) scavenges and neutralizes DPPH˙ (IC50 = 15.6 µmol L-1), ABTS˙+ (IC50 = 5.65 µmol L-1), peroxyl radical (IC50 = 5.64 µg L-1) and 1O2 (IC50 = 0.7 µg m-1). Mg(phen)(fer) effectively protects riboflavin (Rf) against photodegradation by quenching the singlet excited states of Rf regardless of the conditions. Also, the complex Mg(phen)(fer) was effectively incorporated into starch films, broadening its applications, as shown by microbiological studies. Thus, Mg(phen)(fer) has high potential for use in Rf-rich foods and to become a new alternative to the synthetic antioxidants currently used.

Optimised return to play: high treatment success rate in core muscle injury with surgical release of the anterior tendon of the rectus abdominis muscle and proximal tenotomy of the adductor longus muscle.

OBJECTIVES: Core muscle injury is a debilitating condition that causes chronic groin pain in athletes, particularly common in soccer players. The condition is characterised by pain in the inguinal region and can lead to a significant number of absences from high-intensity physical activity. It is caused by repetitive overload without proper counterbalance from the abdominal muscles, hip flexors, and adductors in susceptible athletes. Surgical indications for core muscle injury consider cases where non-surgical treatments have not provided sufficient relief. The aim of this study was to assess the results of surgical intervention for core muscle injury using the technique employed by the Sports Medicine Group of (Institute of Orthopedics and Traumatology of Hospital das Clínicas - Universidade de São Paulo). The procedure involves releasing the anterior portion of the tendon of the rectus abdominis muscle near the pubic symphysis, along with proximal tenotomy of the adductor longus muscle tendon. METHODS: This study utilised a consecutive historical cohort analysis of the medical records of 45 male athletes, of which, 75.6% were professional soccer players, who underwent surgical treatment between January 1, 2002, and December 31, 2021. The participants included active athletes aged between 18 and 40 years, with a mean age of 23.9 years, and were diagnosed with myotendinous core muscle injury. These athletes experienced pain in the pubic symphysis and adductor tendon region and had previously undergone medical treatment and physical therapy for a duration of three to six months without significant improvement. RESULTS: The average time for athletes to return to sport after surgery was 135 days, with a majority of participants being soccer and futsal players. The surgical intervention yielded promising results, with a positive correlation between unilateral injuries and the time taken to return to sport. The complication rate was low, at 6.7%. Notably, the rate of symptom resolution was high, at 93.3%. Furthermore, the analysis indicated that the player's position on the field significantly influenced the discharge period, suggesting that the game position plays a role in the recovery process. CONCLUSION: The combined surgical procedure involving the release of the rectus abdominis tendon and adductor longus muscle tenotomy demonstrates favourable outcomes for athletes with core muscle injury. This study provides strong support for the effectiveness of this surgical approach in managing the condition and offers a potential path to recovery and return to sports activities. STUDY DESIGN: Cross-sectional study.

Espiritualidade e religiosidade na prática médica em um hospital universitário / Spirituality and religiosity in medical practice at a university hospital / Espiritualidad y religiosidad en la práctica médica en un hospital universitario

Resumo A religiosidade e a espiritualidade desempenham papéis cruciais na medicina, especialmente na abordagem centrada no paciente, melhorando a relação médico-paciente. Apesar disso, muitos médicos ainda subutilizam esses recursos, muitas vezes devido a insegurança ao lidar com a esfera pessoal da vida dos pacientes. Para abordar essa questão, conduziu-se pesquisa com 128 médicos, incluindo residentes, em um hospital universitário de Minas Gerais, entre agosto e dezembro de 2021, mediante aplicação dos questionários Inventário de Religiosidade de Duke e Escala Multidimensional de Reatividade Interpessoal, além de questões levantadas em estudos anteriores sobre saúde e espiritualidade. Com isso, buscou-se avaliar de que forma profissionais percebem a importância da religiosidade e da espiritualidade na prática clínica e sua relação com posturas éticas e humanistas. Os resultados revelaram correlação significativa entre as duas escalas, indicando associação positiva entre religiosidade e espiritualidade e empatia.

Abstract Religiosity and spirituality are pivotal in medical practice, particularly in fostering a patient-centered approach that enhances the physician-patient relationship. Despite this, many physicians still underutilize these invaluable resources, often due to feelings of uncertainty when navigating the personal aspects of patients' lives. To address this challenge, a survey involving 128 physicians, including residents, was conducted at a university hospital in Minas Gerais between August and December 2021. Utilizing the Duke Religiosity Inventory and Multidimensional Interpersonal Reactivity Scale questionnaires, alongside inquiries drawn from prior studies on health and spirituality, the goal was to assess professionals' perceptions of the significance of religiosity and spirituality in clinical practice and their interplay with ethical and humanistic attitudes. The findings unveiled a significant correlation between the two scales, underscoring a positive connection between religiosity, spirituality, and empathy.

Resumen La religiosidad y la espiritualidad desempeñan un papel clave en la medicina, especialmente en el enfoque centrado en el paciente al mejorar la relación médico-paciente. Muchos médicos aún no utilizan este recurso, debido a la inseguridad a menudo de enfrentar la vida personal de los pacientes. En este estudio se aplicó a 128 médicos y residentes de un hospital universitario de Minas Gerais (Brasil) los cuestionarios Índice de Religiosidad de Duke y Índice de Reactividad Interpersonal Multidimensional entre agosto y diciembre de 2021, así como preguntas planteadas en estudios anteriores sobre salud y espiritualidad. Se pretendió evaluar la percepción de los profesionales sobre la importancia de la religiosidad y la espiritualidad en la práctica clínica y su relación con las actitudes éticas y humanistas. Los resultados revelaron una correlación significativa entre las dos escalas, lo que indica una asociación positiva entre la religiosidad y espiritualidad y la empatía.

Spontaneous Pneumomediastinum: A Rare Cause of Chest Pain.

Spontaneous pneumomediastinum is a rare medical condition characterized by the presence of free air in the mediastinum, not preceded by trauma, surgery, or another medical procedure. It predominantly affects young adult males and usually has a benign course, and in most cases, it is not possible to identify the precipitating factor. There are some conditions that predispose to its occurrence, namely those that lead to an increase in intrapleural pressure, such as coughing, vomiting, or vigorous exercise. We report a case of a 21-year-old male who presented with acute-onset shortness of breath after an episode of coughing and was found to have mediastinal and subcutaneous emphysema. Clinical, laboratory, and radiological studies did not demonstrate any predisposing factor, and the case was classified as spontaneous pneumomediastinum.

Pharyngocutaneous Fistula Following Total Laryngectomy: a High-Volume Tertiary Centre Series.

Pharyngocutaneous fistula is the leading complication following total laryngectomy. It delays complementary treatments, speech rehabilitation and oral feeding. Despite evolving medical care, fistula incidence remains high. There is no consensus regarding risk factors for fistula development. A standard score for fistula prediction is lacking. Study population included all patients submitted to total laryngectomy (with or without pharyngectomy) due to laryngeal or hypopharyngeal tumours, occurring between January 1st, 2012, and December 31st, 2016. Patient demographics were recorded as well as disease and treatment variables. Statistical analysis was performed using the IBM SPSS Statistics 25®. A previously described predictive model for fistula occurrence was applied. A total of 212 patients were included, the vast majority with advanced local disease (97.5%). Only 10% were submitted to rescue surgery. Fistula incidence was 39.9%. Our rates of locally advanced tumours, with extensive hypopharyngeal involvement, were higher than in most series. Age, tumour location, diabetes, previous chemoradiotherapy, advanced local and regional disease, extensive pharyngectomy, flap reconstruction, manual suture and low post-operative albumin level were associated to fistula occurrence on univariate analysis. Only salvage surgery and advanced local disease remained significant on multivariate analysis. An adapted Cecatto score correlated with fistula occurrence but has not achieved statistical significance. Predictive models for fistula occurrence are lacking. Cecatto score showed promising results in our population but large multicentric studies are necessary for cut-off adjustments.

Risk factors for fibrosis progression in non-alcoholic steatohepatitis: Analysis of the European cohort in the real-world GAIN study.

OBJECTIVE: To better understand drivers of disease progression in non-alcoholic steatohepatitis (NASH), we assessed clinical and sociodemographic markers of fibrosis progression in adults with NASH. PATIENTS AND METHODS: Physician-reported patient demographics and clinical characteristics were utilised from the real-world Global Assessment of the Impact of NASH (GAIN) study. Factors associated with likelihood of fibrosis progression since NASH diagnosis were identified using a logistic regression model. RESULTS: Overall, 2349 patients in Europe from the GAIN study were included; mean age was 54.6 years and 41% were women. Significant covariates included age, years since diagnosis, employment status, fibrosis stage at diagnosis, type 2 diabetes mellitus, hypertension, liver transplant and liver biopsy at diagnosis. Risk of progression was 1.16 (95% confidence interval 1.12-1.20; p<0.001) times higher for each additional year since NASH diagnosis and 5.43 (2.68-11.37; p<0.001) times higher when physicians proposed a liver transplant at diagnosis. Compared with full-time employed patients, risk of progression was 1.77 (1.19-2.60; p=0.004) times higher for unemployed patients and 3.16 (1.30-7.63; p=0.010) times higher for those unable to work due to NASH. CONCLUSIONS: Disease duration, NASH severity and presence of other metabolic comorbidities could help to assess risk of progression in patients with NASH.

Risk prediction in patients with classical low-flow, low-gradient aortic stenosis undergoing surgical intervention.

Introduction: Classical low-flow, low-gradient aortic stenosis (LFLG-AS) is an advanced stage of aortic stenosis, which has a poor prognosis with medical treatment and a high operative mortality after surgical aortic valve replacement (SAVR). There is currently a paucity of information regarding the current prognosis of classical LFLG-AS patients undergoing SAVR and the lack of a reliable risk assessment tool for this particular subset of AS patients. The present study aims to assess mortality predictors in a population of classical LFLG-AS patients undergoing SAVR. Methods: This is a prospective study including 41 consecutive classical LFLG-AS patients (aortic valve area ≤1.0 cm2, mean transaortic gradient <40 mmHg, left ventricular ejection fraction <50%). All patients underwent dobutamine stress echocardiography (DSE), 3D echocardiography, and T1 mapping cardiac magnetic resonance (CMR). Patients with pseudo-severe aortic stenosis were excluded. Patients were divided into groups according to the median value of the mean transaortic gradient (≤25 and >25 mmHg). All-cause, intraprocedural, 30-day, and 1-year mortality rates were evaluated. Results: All of the patients had degenerative aortic stenosis, with a median age of 66 (60-73) years; most of the patients were men (83%). The median EuroSCORE II was 2.19% (1.5%-4.78%), and the median STS was 2.19% (1.6%-3.99%). On DSE, 73.2% had flow reserve (FR), i.e., an increase in stroke volume ≥20% during DSE, with no significant differences between groups. On CMR, late gadolinium enhancement mass was lower in the group with mean transaortic gradient >25 mmHg [2.0 (0.0-8.9) g vs. 8.5 (2.3-15.0) g; p = 0.034), and myocardium extracellular volume (ECV) and indexed ECV were similar between groups. The 30-day and 1-year mortality rates were 14.6% and 43.8%, respectively. The median follow-up was 4.1 (0.3-5.1) years. By multivariate analysis adjusted for FR, only the mean transaortic gradient was an independent predictor of mortality (hazard ratio: 0.923, 95% confidence interval: 0.864-0.986, p = 0.019). A mean transaortic gradient ≤25 mmHg was associated with higher all-cause mortality rates (log-rank p = 0.038), while there was no difference in mortality regarding FR status (log-rank p = 0.114). Conclusions: In patients with classical LFLG-AS undergoing SAVR, the mean transaortic gradient was the only independent mortality predictor in patients with LFLG-AS, especially if ≤25 mmHg. The absence of left ventricular FR had no prognostic impact on long-term outcomes.

Risk Factors for Pharyngocutaneous Fistula Following Total Laryngectomy.

Pharyngocutaneous fistula is the leading complication following total laryngectomy. It delays complementary treatments, speech rehabilitation and oral feeding. Despite evolving medical care, fistula incidence remains high. There is no consensus regarding which patients are at higher risk for fistula development. This article comprised a literature review about risk factors for fistula development. All articles published on an on-line database (PUBMED™) using MESH terms "larynx cancer" and "fistula" in a 5-year period (January 1st, 2014 to January 27th, 2019) were included. Further articles were selected due to expert suggestion by one of the senior surgeons. Only articles written in Portuguese or English were included. Animal studies were excluded. 151 articles were selected and abstracts analysed. 82 articles were selected for full text revision. 32 were later excluded because they described single clinical cases, experimental surgical technics, irrelevant data or poor methodology. Final selection comprised 50 studies: 9 systematic reviews, one non-systematic review, 34 unicentric and 4 multicentric retrospective analysis and two prospective studies. There is no consensus regarding risk factors for fistula development. Patients submitted to salvage surgery for advanced disease seem to be at greater risk. Bad nutritional status is a logical contributor, but the ideal surrogate marker is still missing. Several variables are inconsistently pointed as risk factors and should be abandoned unless proved otherwise. There are no standard scores for fistula occurrence despite being a common complication following surgery.

How well are Brazilian mastologists (breast surgeons) trained in breast reconstruction and oncoplastic surgery? A study of the impact of a breast reconstruction and oncoplastic surgery improvement course.

Introduction: The breasts are a female symbol, impacts self-image and self-esteem. Breast reconstructive and oncoplastic surgeries have an important role in minimizing injuries. In Brazil less than a third of public health system (SUS) users have access to immediate reconstructive surgery. The low rate of breast reconstructions has multiple causes and the deficiency in availability and surgeons' technical qualification play a role. In 2010, the Breast Reconstruction and Oncoplastic Surgery Improvement Course was created by professors of the Mastology Department of Santa Casa de São Paulo and State University of Campinas (UNICAMP). The objectives of this study were to evaluate the impact of the techniques learned on patients' management by the surgeons enrolled in the Course, as well as to characterize their profile. Methods: All students enrolled in the Improvement Course between 2010 and 2018 were invited to answer an online questionnaire. Students who did not agree to answer the questionnaire or answered them incompletely were excluded. Results: Total students included: 59. The mean age: 48.9 years, male (72%) with more than 5 years of Mastology practice (82.2%), from all regions of Brazil, 1.7% from the North, 33.9% from the Northeast, 44.1% from the Southeast, and 12% from the South. Most of the students considered they had little or no knowledge of breast reconstruction (74.6%) and 91,5% did not consider they had enough aptitude to perform breast reconstructions after finishing residency. After the Course, 96.6% considered themselves apt to perform such surgeries. Over 90% of the students considered the Course had impacted their practice and changed their surgical strategy view. Before the Course, 84.8% of the students stated that less than half of their patients who were operated on for breast cancer had breast reconstruction, compared to 30.5% after the Course. Conclusion: The Breast Reconstruction and Oncoplastic Surgery Improvement Course studied here positively impacted the mastologists' management of patients. New training centers worldwide can help a lot of women with breast cancer.

Beyond Pain Relief: A Review on Cannabidiol Potential in Medical Therapies.

The phytocannabinoid cannabidiol (CBD) is receiving increasing attention due to its pharmacological properties. Although CBD is extracted from Cannabis sativa, it lacks the psychoactive effects of Δ9-tetrahydrocannabinol (THC) and has become an attractive compound for pharmacological uses due to its anti-inflammatory, antioxidant, anticonvulsant, and anxiolytic potential. The molecular mechanisms involved in CBD's biological effects are not limited to its interaction with classical cannabinoid receptors, exerting anti-inflammatory or pain-relief effects. Several pieces of evidence demonstrate that CBD interacts with other receptors and cellular signaling cascades, which further support CBD's therapeutic potential beyond pain management. In this review, we take a closer look at the molecular mechanisms of CBD and its potential therapeutic application in the context of cancer, neurodegeneration, and autoimmune diseases.

Postoperative myocardial fibrosis assessment in aortic valvular heart diseases-a cardiovascular magnetic resonance study.

AIMS: Left ventricular remodelling occurs during the chronic course of aortic regurgitation (AR) and aortic stenosis (AS), leading to myocardial hypertrophy and fibrosis. Several studies have shown that extracellular volume fraction (ECV) and indexed extracellular volume (iECV) are important surrogate markers of diffuse myocardial fibrosis (MF). Postoperative data on these cardiovascular magnetic resonance (CMR) extracellular expansion parameters for either AS or AR are scarce. This study aimed to demonstrate the postoperative changes that occur in diffuse MF, and the influence of preoperative MF on the reversal of LV remodelling, in patients with AR or AS. METHODS AND RESULTS: Patients with severe AR or AS and indications for surgery were prospectively enrolled. Patients underwent pre- and postoperative CMR, and ECV and iECV were quantified. Data from 99 patients were analysed (32 with AR and 67 with AS). After surgery, the left ventricle mass index decreased in both groups (AR: 110 vs. 91 g/m2; AS: 86 vs. 68 g/m2, both P < 0.001). The late gadolinium enhancement fraction (AR: preoperative 1.9% vs. postoperative 1.7%, P = 0.575; AS: preoperative 2.4% vs. postoperative 2.4%, P = 0.615) and late gadolinium enhancement mass (AR: preoperative 3.8 g vs. postoperative 2.5 g, P = 0.635; AS: preoperative 3.4 g vs. postoperative 3.5 g, P = 0.575) remained stable in both groups. Preoperative iECV and ECV were greater in the AR group (iECV: 30 mL/m2 vs. 22 mL/m2, P = 0.001; ECV: 28.4% vs. 27.2%, P = 0.048). Indexed extracellular volume decreased after surgery in both groups (AR: 30-26.5 mL/m2, AS: 22-18.2 mL/m2, both P < 0.001); it was still greater in the AR group (AR: 26.5 mL/m2 vs. AS: 18.2 mL/m2, P < 0.001). Postoperative ECV remained stable in the AR group (preoperative 28.4% vs. postoperative 29.9%; P = 0.617) and increased in the AS group (preoperative 27.2% vs. postoperative 28.6%; P = 0.033). CONCLUSION: Patients with both AR or AS presented reduction in iECV after surgery, unfolding the reversible nature of diffuse MF. In contrast to patients with AS, those with AR developed postoperative iECV regression with stable ECV, suggesting a balanced reduction in both intracellular and extracellular myocardial components.

Esterification of p-Coumaric Acid Improves the Control over Melanoma Cell Growth.

Previous studies reported that p-coumaric acid modulates melanoma growth. Because the esterification of p-coumaric acid (p-CA) enhanced its activity as an antimelanogenic agent, we aimed to determine the antitumor potential of two derivatives, the ethyl and butyl esters, against the murine B16-F10 and the human SK-MEL-25 melanoma cells. Cell viability was determined in vitro by the lactate dehydrogenase release and violet crystal absorption assays. The cell proliferation rate and cell cycle behavior were determined by the colony formation assay and flow cytometry analysis. Although p-CA, at the concentration of 1 mM, failed to exert a significant antitumor activity, the ethyl and butyl ester derivatives caused substantial tumor cell death at doses < 1 mM. Despite a reduction in their direct cytotoxicity at minor doses, both products controlled the melanoma growth by arresting the cell cycle at the G0/G1 (B16-F10) or S/G2 (SK-MEL-25). Furthermore, the in vivo experiments showed that the butyl ester derivative suppressed the lung B16-F10 burden, compared to the p-CA-treated mice. Thus, the esterification of p-coumaric acid improved the control over the proliferation of murine and human melanoma cells and can be considered an approach for designing novel anticancer agents.